Abstract

New oral anticoagulants, including dabigatran, rivaroxaban, and apixaban, have been
recently approved for primary and secondary prophylaxis of thromboembolic conditions.
However, there is no clear strategy for managing and reversing their anticoagulant
effects. We aimed to summarize the available evidence for clinical management and
reversal of bleeding associated with new oral anticoagulants. Using a systematic review
approach, we aimed to identify studies describing reversal strategies for dabigatran,
rivaroxaban, and apixaban. The search was conducted using Medline, EMBASE, HealthSTAR,
and grey literature. We included laboratory and human studies. We included 23 studies
reported in 37 out of 106 potentially relevant references. Four studies were conducted
in humans and the rest were in vitro and in vivo studies. The majority of the studies evaluated the use of prothrombinase complex concentrate
(PCC), either activated or inactivated, and recombinant activated factor VII (rFVIIa).
Other interventions were also identified. Laboratory studies suggest that hemostatic
parameters and bleeding might be partially or completely corrected by PCC for rivaroxaban
better than dabigatran. Studies in humans suggest that PCC might reverse the effects
of rivaroxaban better than dabigatran assessed by hemostatic tests. We were not able
to locate studies evaluating the clinical efficacy of these agents. The best available
evidence suggests that PCC (activated or inactivated) might be the best option for
reversing new anticoagulants. Evidence for rFVIIa is less compelling. There might
be differences in the efficacy of reversing agents for different anticoagulants. Studies
assessing the clinical efficacy of these reversal agents are urgently needed.